Numerous bacterial pathogens, particularly those that colonize fast flow areas in the bladder and gastrointestinal (GI) tract, require motility to establish infection and subsequently spread within the initially colonized tissue. For instance, flagellum has been recognized as a major virulent factor in Campylobacter jejuni, which annually causes 2.5 million cases of diarrhea (Guerry 1994). In Salmonella enteritidis serovar Typhimurium, the interaction between released flagellin and Toll-like receptor 5 is a major component of the inflammatory response conducive to enteritis (Carlo and Podolsky 2003, McCormick 2003). In V. cholerae, motility is required for intestinal colonization and spreading of the infection along the GI tract (Lee et al. 2002, Silva et al. 2006).
Cholera is an acute water-borne diarrheal disease caused by V. cholerae of serogroups O1 and O139. Cholera continues to be a major public health concern in endemic areas of south Asia and Africa. The disease generally presents itself in the form of rapidly spreading outbreaks and is a common sequel of natural disasters such as hurricanes, tsunamis, flooding and earthquakes. In 2009, 221,226 laboratory-confirmed cholera cases and 4946 deaths were reported to the World Health Organization (WHO) (Cholera 2009). However, a more realistic estimate of the prevalence of cholera is 5.5 million cases and 130,000 deaths per year. The emergence of multiple antibiotic resistant V. cholerae O1 and O139 strains has been recognized as a major concern (Das et al. 2008, Mwansa et al. 2007, Okeke et al. 2007, Roychowdhury et al. 2008). Oral inactivated whole cell and live genetically-attenuated vaccines are currently under intense evaluation. Nevertheless, the capacity of these vaccines to contain rapidly spreading cholera outbreaks is under debate and their use for this purpose is not recommended by the WHO. Furthermore, the deployment of cholera vaccines in isolated regions still poses significant logistic challenges. The availability of new prophylactic and/or therapeutic agents is required to diminish the burden of cholera. The hallmark of V. cholerae strains that cause epidemic cholera is the production of two major virulence factors: cholera toxin and the toxin-coregulated pilus. Cholera toxin is responsible for the profuse watery diarrhea and the toxin-coregulated pilus is required for intestinal colonization (Finkelstein 1992, Kaper et al. 1995). Strains in which the genes encoding these virulence factors have been deleted are avirulent.